PDE4B x A1R x A2aR

Treatment of Dentin Hypersensitivity Using Theobromine , Remin Pro , and Combination of Both Materials

Rationale: Despite successful efforts to lower atherogenic serum low-density lipoprotein (LDL) cholesterol concentrations, a substantial residual cardiovascular risk remains. An additive strategy to further lower this residual risk may be via raising high-density lipoprotein (HDL) concentrations, and in particular those of its major protein constituent apolipoprotein A-I (apoA-I). Based on several studies, theobromine may be a promising candidate in this respect. Recently, theobromine was shown to increase serum HDL cholesterol (HDL-C) concentrations by 0.16 mmol/L or 10% and apoA-I levels with 8%. The question is whether this increase in HDL-C and apoA-I concentrations observed translates into an improved functionality of the blood vessels. Effects of theobromine on vascular function have never been evaluated in a placebo controlled human intervention study.
Objective: The primary objective is to evaluate the long-term effects of theobromine on vascular function in healthy subjects with a slightly lowered HDL-C in the fasting and the postprandial state. The second primary objective is to evaluate the long-term effects of theobromine on intestinal apoA-I mRNA and protein expression levels in healthy subjects with a slightly lowered HDL-C in the fasting and the postprandial state.
Secondary objectives are to study the long-term effects of theobromine on (1) fasting serum HDL-C concentrations, (2) cholesterol efflux capacity and (3) postprandial lipid and glucose metabolism.
Study design: A randomized, double-blind, placebo controlled cross-over design. The total study duration will be 12 weeks, consisting of a 4 week experimental period, a 4 week wash-out, and a 4 week control period. At the end of the experimental and control periods, a postprandial test will take place.
Study population: Forty-eight healthy men aged 45-70 years and women aged 50-70 years, with slightly lowered HDL-C concentrations (men <1.3 mmol/L and women <1.5 mmol/L).
Intervention: During the experimental period, subjects will consume daily at breakfast an drink containing 500 mg theobromine. During the placebo period, the subjects will consume daily at breakfast the same drink without theobromine. During the wash-out period, they will not consume any of the drinks.
Main study parameters/endpoints: Measurements will be performed at the end of both 4-week intervention periods. The effects of theobromine will be calculated as the absolute differences between values obtained at the end of each period. The primary endpoint is the change in vascular function defined as % change in flow-mediated dilation (FMD) after intake of a daily stressor, a milkshake providing all the three different macronutrients. The second primary endpoint is the change in apoA-I mRNA and protein expression on the end of each period 5 hours after intake of the milkshake.